EpigeneticPrepared by

Ala’a Alruwaisan_Sumaiah AlghamdiNorah Alhoshani_ Hend Alsubaie

Submitted to _Dr. Zainab

18_12_2014

Objectives _Introduction.

_Epigenetic structure. _Epigenetic mechanisms.

_Behavioral epigenetic .

introduction _You are what your mother ate!

_Twins have the same genes but why one of them has specific disease and another dose not!

_What is the cause of increasing the percentage of some diseases?

_epigenetic is a recent science .

History of Epigenetics_1940s Conrad Waddington had defined

epigenetics as the “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype

into being ”._1948 DNA methylation was first described in

bacterial genomes. _1975 ,two groups independently did hypothesize

that 5-methylcytosines were duplicated through cell division and regulated mRNA expression.

History of Epigenetic _1975 ,Allfrey et had already demonstrated

that histone acetylation and methylation contributed to gene expression control .

_1990s, Andrew Feinberg, “epicenter of modern medicine because it can help to explain the relationship between an individual's genetic background, the

environment, aging, and disease ”.

Epigenetic definitionEpigenetic definitionEpigenetics is the study of heritable alterations in phenotypes and gene expression that occur without changes in the DNA sequence.

Epigenetic mechanisms are flexible genomic factors:

1-Because it can change genome function under exogenous influence.

2 _It can provide a molecular substrate that allows for the stable propagation of gene expression states from one generation of cells to the next.

Epigenetic impactThere is relationship between epigenetic changes and a host of disorders including:

_Various cancers._Mental retardation associated disorders.

_Immune disorders._Neuropsychiatric disorders.

_Pediatric disorders.

Epigenetic avoidanceCan We Keep Our Epigenome Healthy? How Can We Get It Back in Shape? _A growing sector of pharmacological research has focused on the development of drugs that can modify the epigenome. For instance, animal experiments have identified histone deacetylase inhibitors.A major issue in epigenomic is how rapidly and how effectively these epigenomic drugs can be translated to humans and introduced in standard clinical practice.

Epigenetic factorsThere are at least three systems which are:

1 _DNA methylation.2 _Histone modification.

3 _Non-coding RNA (ncRNA)associated gene silencing are currently considered to initiate and sustain epigenetic change.

Place of occurrence of epigenetics

• A adjustments occur in gene function without any change in

the nucleotide sequences that make up DNA.

• On-DNA inheritance or epigenetics means that the sequence of

the DNA doesn’t change, but access to the DNA changes

biochemically. This altered DNA can transfer to children and

grandchildren.

Genes structure

Gene occurs when the impact of external factors

• Aware of epigenetic a new and important level of our

understanding of heredity and the impact of the environment

on human reason

• . Indicates that some things in human life , such as the type

and quantity of nutrition , anxiety and exposure to toxins and

many other things that could have an effect on the organism is

inherited from one generation to another generation.

Identified those factors in several points

• Environmental factors• Behavioral factors• Dietary factors• Psychological factors

How occurrence epigenetic Two ways:

Amendments to DNA

methylation

Histone modificat

ionAcyetalit

ionDetour

dna

Amendments to DNA methylationWhat is DNA methylation?

adding a methyl molecule into cytosine base in the DNA.what is their role ? Or effect?

 Methylation has the ability to inhibit or activate gene.

  *For that to happen?

it is explained as epigenetics which is changes in DNA without any change in the genetic sequence.

How it is happen

• Consisted of methyl carbon and three atoms of hydrogen and has a strong tendency to link to something else (ie Methylth ) . And the methyl group has affinity cytosine bases in DNA .

• there are a special enzymes derivative of methyl molecules which essential nutrients , such as folic acid, and vitamin B12, and it control by certain rules in the genome

Amendments to DNA methylation

Amendments to DNA methylation

• And explain to add or Methylthed of DNA in the

back bone affect the genetic structure leads to

increase access to Methylthed IN hydrogen bonds

between DNA strands and thus the changing of

DNA lead to the silence the gene expression by

preventing adhesion of expression enzymes.

• The presence of methylation by gene prevents enzymes from link to it and therefore not be read not identify him

Histone modification

How it is work?

Modification occurs in two ways for histone

1- Acyetalition

Changes occur in histone by the addition or removal of

Acetyl group which work to amplify the genes to create

the occurrence of gene expression.

Acyetalition

• changes in histone because of influencing factors leads to the entry of the dehydrogenase acetyl enzymes thus changing the composition and thus disarming acetyl which considered as important factor in gene expression leads to stopped gene and silence the gene

• The histone complex chemical markers attached to the ends of tails of histones controls the gene expression

• . Usually signs of acetylcholine signs Colin acetyl exaggerating the neighboring genes , While enzymes with claims of acetylcholine stop gene

Histone modification2 -wrap DNA

• 2- wrap DNA When the DNA wrapped around the histone

strong leadership to stop the narrow gene expression by

blocking enzymes up to the protein ,

• and a change in the gene structure

• When the Dna wrapping around the histone heavily then

enzymes cannot be accessed for Histone .

Histone modification

Epigenetic & Disease

Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and micro RNAs (mi RNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches.

Epigenenatic influence

Nutrition and the Epigenome

Nutrient Food Origin Epigenetic Role

MethionineSesame seeds, brazil nuts, fish, peppers,

spinachSAM synthesis

Folic AcidLeafy vegetables, sunflower seeds,

baker's yeast, liverMethionine synthesis

Vitamin B12 Meat, liver, shellfish, milk Methionine synthesis

Vitamin B6Meats, whole grain

products, vegetables, nuts

Methionine synthesis

SAM-e (SAM)Popular dietary supplement pill; unstable in food

Enzymes transfer methyl groups from SAM directly to the

DNA

CholineEgg yolks, liver, soy,

cooked beef, chicken, veal and

turkeyMethyl donor to SAM

BetaineWheat, spinach,

shellfish, and sugar beets

Break down the toxic byproducts of SAM

synthesis

Nutrition and the Epigenome

Nutrient Food Origin Epigenetic Role

Resveratrol Red wineRemoves acetyl

groups from histones, improving health

(shown in lab mice)

Genistein Soy, soy productsIncreased methylation,

cancer prevention, unknown mechanism

Sulforaphane BroccoliIncreased histone

acetylation turning on anti-cancer genes

ButyrateA compound produced in the intestine when

dietary fiber is fermented

Increased histone acetylation turning on

'protective' genes, increased lifespan

(shown in the lab in flies)

Diallyl sulphide (DADS) Garlic

Increased histone acetylation turning on

anti-cancer genes

Nutrition and the Epigenome

Disease ExamplesGene Disease

Xq28 sexual orientation 1993 1E2F Rb Retinoblastoma 2P53 Li-Fraumeni Syndrome 3

Behavioral Epigenetic

Behavioral Epigenetic• One Branch OF Epigenetic is development of

behavior its name: Behavioral Epigenetic• refers to the study of how signals from the

environment trigger molecular biological changes that modify what goes on in brain cells.• it is Includes everything that happens in every

stage of life and It has a relationship to environment such as: social experience; nutrition; hormones; and toxicological exposures that occur prenatally, postnatally, and in adulthood.

Short Story

Experiment • the Researchers kerry ressler

and brian dias From Emory University in

Atlanta discovered a special discovery that the DNA can transfer the memories until the 3rd generation !!

Experimentsteps:

1- Male mice were adapted to be afraid from specific smell ..

he let 12 male mice face light electric shocks directly after being smell specific chemical molecule (Acetophenone ) five times a day during

the three days..

Experiment steps:the result :males learned fear by linking

electrical shock and smell

2-the male Mated with the female was not subject to adaptation

After ten days ,happen a Mating between males and females " never exposed to the smell of acetophenone“

then they were separated to avoid

the exchange of informationbetween males and females.

Experiment steps:

3-Young people grew up without a father and without adaptation,the female is caring for the babies

To avoid allowing the exchange of information between the male and young, which has

never exposed to acetophenone

during growth.

Experiment steps:

4- At pubertyoffspring exposed to

acetophenone with non adaptation offspring male the reuslt they Showed a greater tendency to fear

Experiment steps:

Explanation:In this examples which based on fear Conditioning There are tow Explanation:

1 -J. David Sweatt, director of the McKnight Brain Institute at the University of Alabama at Birmingham,• Forming memories of and remembering this fear

is raise acetylation of histones in the hippocampusWhich interferes with the behavior usually

associated with the fear.• but blocking acetylation reverses these effects

and also strengthens the formation of the fear memories

Explanation:2- Michael Meaney and of

Douglas Hospital in Montreal, and Eric Nestler at Mount Sinai in New York City says:

• is just the opposite , At least a subset of genes undergo active demethylation and remethylation, which is driven by the environment or by experience.

• This dynamism, he says, can lead to either transient or persistent functional changes in the nervous system

Explanation:• It's reasonable to think that

these transgenerational effects will have a half life, so to speak, that they probably last for two, three, four generations and then are subject to reversing back to the original baseline state.

Future revolution• .epigenetics is already a vast topic, rife with

complexities that grow more intricate every day. Discoveries seem to lead not to illumination but to more questions,

• and we have space here to touch on barely a few. ,it perhaps solve for immense medical troubles. at some future date seems likely to potentially fix (or even prevent) mental disorders and Somatic disorders.

• how long will it be before we try our hand at such epigenetic improvements??

References• Epigenetic Changes in Cancer• Epigenetics and Autoimmune Diseases• Epigenetics in BIOLOGY and MEDICINE• The RB Epigenetic Functions in Cancer Progression Control

2013• http://circgenetics.ahajournals.org/content/3/6/567.full• http://bioscience.oxfordjournals.org• ADN IL TRANSMET AUSSI NOS SOUVENIRS!, Science &vie 1158

pp 72-75• http://publications.kacst.edu.sa

References

• http://www.oloommagazine.com • Riggs, A. D., Martiennssen, R. A. & Russo,

V. E. A. in• Epigenetic Mechanisms of Gene Regulation

1–4•(Cold Spring Harbor Laboratory Press, Cold Spring•Harbor, New York, 1996).

Thanks